Does dialysis remove fentanyl (synthetic opioid) or hydromorphone (opioid analgesic) from the body?

Dialysis Removal of Fentanyl and Hydromorphone

Neither fentanyl nor hydromorphone are effectively removed by dialysis, but fentanyl is the safer choice in dialysis patients due to the absence of active metabolites, while hydromorphone requires cautious use with close monitoring due to accumulation of its active metabolite (hydromorphone-3-glucuronide) between dialysis sessions. 1

Fentanyl and Dialysis

Fentanyl is NOT removed by dialysis and is considered one of the safest opioids for patients with renal failure. 1

• Fentanyl undergoes primarily hepatic metabolism with minimal renal clearance and produces no active metabolites that accumulate in renal failure 1, 2
• The drug is highly lipid-soluble and distributes extensively into fat tissue, which can prolong its effects but does not create toxic metabolite accumulation 1, 2
• Multiple international guidelines (ESMO, Intensive Care Medicine) specifically recommend fentanyl as a preferred opioid in patients with chronic kidney disease stages 4-5 (GFR <30 mL/min) or those on dialysis 1
• No dose reduction is required for fentanyl in dialysis patients, though careful titration is still warranted 3, 4

Clinical Implications for Fentanyl

• Start with lower IV doses (25-50 μg) in dialysis patients, particularly if elderly or debilitated 2
• Transdermal fentanyl is the preferred formulation for stable pain control in dialysis patients 1, 2
• The lack of dialyzability is actually advantageous—it provides stable analgesia without the need for supplemental dosing after dialysis sessions 4

Hydromorphone and Dialysis

Hydromorphone should be used cautiously in dialysis patients because while the parent drug is partially removed by dialysis, its active metabolite (hydromorphone-3-glucuronide, H3G) accumulates significantly between dialysis treatments. 1, 5

Pharmacokinetic Evidence

• Research demonstrates that H3G accumulates extensively between hemodialysis sessions (accumulation factor R = 12.5), though it is effectively removed during dialysis itself (reduction factor 1.8) 5
• The parent drug hydromorphone does not substantially accumulate (R = 2.7) due to rapid conversion to H3G 5
• Hydromorphone plasma concentrations decrease by approximately 55% during hemodialysis, compared to only 15% for methadone 6
• The mean plasma clearance of hydromorphone during dialysis is 105.7 mL/min, indicating significant dialytic removal 6

Clinical Implications for Hydromorphone

• The accumulation of H3G between dialysis sessions is associated with increased sensory-type pain (correlation r = 0.76) and reduced duration of analgesia 5
• If hydromorphone is used, dose reduction and extended dosing intervals are mandatory 1, 3
• Close monitoring for opioid toxicity is essential, particularly in the 24-48 hours before the next dialysis session when H3G levels peak 5
• International guidelines recommend hydromorphone be used "cautiously" with an active metabolite that "can accumulate between dialysis treatments" 1

Comparative Safety Profile

The key distinction is that fentanyl's lack of active metabolites makes it inherently safer than hydromorphone in the dialysis population:

• Fentanyl and methadone are described as "relatively safe in renal failure since they have no active metabolites" and "neither is removed by dialysis" 1
• Hydromorphone falls into an intermediate safety category—safer than morphine or codeine (which should be avoided entirely), but less safe than fentanyl or buprenorphine 1, 4
• Research directly comparing opioid stability during dialysis found methadone (another non-dialyzable opioid) provided more stable plasma concentrations than hydromorphone 6

Practical Algorithm for Opioid Selection in Dialysis Patients

First-line choices (safest, not removed by dialysis):

• Fentanyl (IV or transdermal) 1, 2
• Buprenorphine (transdermal or IV) 1, 7
• Methadone (requires specialist expertise) 1, 6

Second-line with caution (partially dialyzable, metabolite concerns):

• Hydromorphone with reduced doses and extended intervals 1, 5, 3
• Oxycodone with dose reduction 3, 4

Avoid entirely in dialysis patients:

• Morphine (toxic metabolite accumulation) 1, 3
• Codeine (toxic metabolite accumulation) 1, 3, 4
• Meperidine (neurotoxic metabolite normeperidine) 2, 4

Critical Monitoring Points

• Have naloxone readily available regardless of which opioid is chosen 2
• Monitor for neuroexcitatory effects (myoclonus, confusion, hallucinations) which indicate metabolite accumulation 1
• Assess pain control both during and between dialysis sessions, as some opioids may provide unstable analgesia 5, 6
• Watch for respiratory depression, particularly when combining opioids with benzodiazepines 2